c-Met, the receptor of hepatocyte growth factor is known to be responsible for the motility and mitogenesis of epithelial cells including cancer cells. To investigate the significance of c-Met expression in human colorectal cancer (CRC), total cellular protein, extracted from 130 CRCs were examined by Western blot analysis. The signal was quantitated by ChemiImager 4000 Low Light Imaging System. c-Met expression was analyzed as the ratio of tumor to matched normal tissue (T/N) and expressed as fold-increase. The cellular localization of c-Met was assessed by immunohistochemistry. The T/N fold increase of c-Met varied from 0.2 to 10.7 with a mean of 3.41 +/- 0.23 (mean +/- SE). 69% primary CRC showed overexpression (T/N > 2.0) of c-Met. Significantly higher c-Met levels were found in CRC with blood vessel invasion (P = 0.04), and in advanced stage (P = 0.04). No relationship was noted between c-Met expression and age, tumor size, location, differentiation. C-Met immunoreactivity was observed in the membrane and cytoplasm of cancer cells. Positive staining of endothelial cells of blood vessels within normal submucosa and tumor was also evident. C-Met protein is expressed at levels significantly higher than adjacent mucosa in most primary adenocarcinomas of the colon. Our results support an important role for c-Met in human CRC progression and metastasis.